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CNS-infiltrating CD8 T cells become virus-specific and engage neurons during TMEV infection

McDole, Jeremiah Ray
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1258480789

Abstract Details

2010, PhD, University of Cincinnati, Medicine : Neuroscience/Medical Science Scholars Interdisiplinary.
Compelling research has linked CD8 T cells to neuronal injury, a pathological hallmark of multiple sclerosis. The epitopes recognized by CD8 T cells in MS patients remains unknown. Defining these epitopes is of potentially critical importance to developing new therapeutics for MS, an aspect of which has been explored by our lab. In previous studies using the established Theiler's murine encephalomyelitis virus (TMEV) model of MS we demonstrated that expansion of an immunodominant population of CD8 T cells could be inhibited by the administration of the epitope peptide that they recognized. Inhibiting the expansion of this CD8 T cell population resulted in reduced levels of neuronal injury and sparing of motor ability. In work presented here we have developed an unbiased, molecular approach for determining CD8 T cell epitopes using the TMEV model. Such an approach could be potentially translated from this animal model to MS, possibly contributing to future therapeutics. Further, defining the putative mechanism utilized by CD8 T cells to perpetuate neuronal pathology in diseases such as Rasmussen's encephalomyelitis, neurological neoplastic disorders and MS remains a critical topic of research. Defining this mechanism could have important ramifications for the development of new treatments for these conditions. In studies presented here using the TMEV model we demonstrate evidence that strongly suggests CD8 T cells form traditional immune synapses with neurons. Further, we demonstrate that CD8 T cells also polarize granzyme B, an effector molecule that can potentially induce apoptosis, towards target neurons. Taken together this evidence provides a potential mechanism utilized by CD8 T cells to perpetuate neuronal pathology. Lastly, we demonstrate in these studies that morphological changes observed in CD8 T cells are iii associated with movement through CNS tissue. The motility patterns of these CNS infiltrating CD8 T cells was similar to the movement observed in other studies examining T cells within lymph nodes. Such observations may suggest that a common cellular mechanism controls morphological changes and motility among CD8 T cells regardless of the organ within which they are derived.
Aaron Johnson, PhD (Committee Chair)
Istvan Pirko, MD (Committee Member)
David Hildeman, PhD (Committee Member)
Kim Seroogy, PhD (Committee Member)
Steve Danzer, PhD (Committee Member)
157 p.
Immunology; Neurology
Immune synapse; neuron; CD8 T cell; MHC class I; TCR; TMEV

Recommended Citations

Citations

  • McDole, J. R. (2010). CNS-infiltrating CD8 T cells become virus-specific and engage neurons during TMEV infection [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1258480789

    APA Style (7th edition)

  • McDole, Jeremiah. CNS-infiltrating CD8 T cells become virus-specific and engage neurons during TMEV infection. 2010. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1258480789.

    MLA Style (8th edition)

  • McDole, Jeremiah. "CNS-infiltrating CD8 T cells become virus-specific and engage neurons during TMEV infection." Doctoral dissertation, University of Cincinnati, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1258480789

    Chicago Manual of Style (17th edition)

ucin1258480789
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© 2009, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.